WO2018006737A1 - Sel de mangiférine-6-o-calcium et son procédé de préparation et son utilisation - Google Patents

Sel de mangiférine-6-o-calcium et son procédé de préparation et son utilisation Download PDF

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Publication number
WO2018006737A1
WO2018006737A1 PCT/CN2017/090489 CN2017090489W WO2018006737A1 WO 2018006737 A1 WO2018006737 A1 WO 2018006737A1 CN 2017090489 W CN2017090489 W CN 2017090489W WO 2018006737 A1 WO2018006737 A1 WO 2018006737A1
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mangiferin
salt
solution
calcium salt
calcium
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PCT/CN2017/090489
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English (en)
Chinese (zh)
Inventor
滕厚雷
吴巍
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常州德泽医药科技有限公司
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Priority to CN201780027751.4A priority Critical patent/CN109475569B/zh
Priority to JP2018567960A priority patent/JP6783329B2/ja
Priority to EP17823549.5A priority patent/EP3479829A4/fr
Publication of WO2018006737A1 publication Critical patent/WO2018006737A1/fr
Priority to US16/231,960 priority patent/US10538547B2/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H7/00—Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
    • C07H7/06—Heterocyclic radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H7/00—Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
    • C07H7/04—Carbocyclic radicals

Definitions

  • the present invention relates to a mangiferin-6-0-calcium salt and a process for the preparation thereof.
  • mangiferin-6-0-calcium salt as an intermediate in the preparation of mangiferin-6-0-berberine salt.
  • Mangiferin is a natural polyphenolic compound having the formula: C 19 H 18 0 consult, molecular weight: 422, and its chemical structure is as follows:
  • WO 2010/145192 A1 discloses a mangiferin berberine salt according to the specification of WO 2010/145192 A1
  • the nuclear magnetic data analysis disclosed in the second page of page 5 - page 7 is known to be that the mangiferin berberine salt disclosed should be mangiferin-3-0-berberine salt and mangiferin-7-0-small.
  • a composition of a muscarinic salt, but regarding the ratio of mangiferin-3-0-berberine salt to mangiferin-7-0-berberine salt, WO 2010/145192 A1 is not described. technical problem
  • the structure of the drug substance provided by the listed drug must be clear. If the drug substance is a composition, the proportion must also be determined in order to meet the requirements for controllable drug quality. It can be seen that if the mangiferin berberine salt disclosed in W0 2010/145192A1 is used as a raw material drug, it is necessary to solve the problem of further clarifying the structure. By analyzing the structure of mangiferin, it is known that there are four phenolic hydroxyl groups in the molecular structure of mangiferin, so there are many possibilities for the salt formation of mangiferin, which makes the technical difficulty of obtaining mangiferin salt of a single salt-forming site greatly increased.
  • mangiferin raw material is a plant-derived extract, it may be due to plant variety, collection of diurnal or collection areas, and differences in extraction processes, mangiferin analogs such as mangiferin and other impurities such as tannins in mangiferin raw materials.
  • mangiferin raw material is a plant-derived extract
  • mangiferin analogs such as mangiferin and other impurities such as tannins in mangiferin raw materials.
  • the difference in the content between the batches is large; in this case, the preparation method of the mangiferin berberine salt disclosed in WO2010/145192A1 is prepared by using mangiferin raw material to prepare a monosodium (potassium) salt solution of mangiferin, directly with hydrochloric acid.
  • mangiferin berberine salt by berberine solution reaction is very prone to the problem of large difference in mass consistency between batches of mangiferin and berberine salt; the same problem of the accuracy of mangiferin feeding is also present.
  • mangiferin berberine salt is prepared by using mangiferin monosodium (potassium) salt solids, it needs to be precipitated by using a crystal solvent such as ethanol or acetone, which will result in a larger amount of ethanol, acetone, acetic acid in the preparation process.
  • organic solvents such as ethyl esters, which are not only costly, but also increase the solvent residual risk of mangiferin berberine salt, and bring heavy environmental pressures in industrial production.
  • mangiferin-6-0-berberine salt was prepared by using mangiferin-6-0-calcium salt as an intermediate, which solved the problem of poor quality consistency between the preparations of mannin berberine salt.
  • the present invention provides a mangiferin-6-0-calcium salt, characterized in that the mangiferin-6-0-calcium salt has the structure of the following formula (I):
  • alkaline sodium salt or alkaline potassium salt is added to water to prepare an alkaline sodium salt solution or alkaline potassium salt solution, concentration
  • [0018] 2 is added mangiferin dissolved in dimethyl sulfoxide to form a mangiferin solution;
  • the calcium salt solution is fully mixed with the mangiferin sodium salt solution or the mangiferin potassium salt solution, the reaction is complete, the precipitate is precipitated, and filtered to obtain a solid; the solid is dissolved in an appropriate amount of hot water, filtered, and precipitated. , filtered to obtain a solid; [0022] 6 solid matter was dried to obtain mangiferin-6-0-calcium salt.
  • the method for producing mangiferin-6-0-calcium salt according to the present invention is characterized in that the ratio of the mangiferin to dimethyl sulfoxide is 1:0.2-5 (w/v).
  • the method for preparing mangiferin-6-0-calcium salt according to the present invention is characterized in that the molar ratio of the mangiferin to the basic sodium salt or the basic potassium salt is 1:0.5-1.
  • the method for producing mangiferin-6-0-calcium salt according to the present invention is characterized in that the molar ratio of the mangiferin to the water-soluble calcium salt is 1:0.5-1.
  • the preparation method of the mangiferin-6-0-calcium salt according to the present invention is characterized in that the basic sodium salt or the basic potassium salt is selected from the group consisting of sodium carbonate, sodium hydrogencarbonate, potassium carbonate and hydrogen carbonate.
  • the basic sodium salt or the basic potassium salt is selected from the group consisting of sodium carbonate, sodium hydrogencarbonate, potassium carbonate and hydrogen carbonate.
  • One or a mixture of two or more of potassium selected from the group consisting of calcium chloride, calcium gluconate, calcium lactate, calcium ketobutyrate, or a mixture of two or more thereof.
  • the mangiferin-6-0-calcium salt obtained by the present invention may be a hydrate containing less than 9 water per molecule of mangiferin-6-0-calcium salt.
  • mangiferin-6-0-calcium salt of the present invention as an intermediate in the preparation of mangiferin-6-0-berberine salt (formula):
  • the specific method for preparing the mangiferin- 6 __ berberine salt by using the mangiferin-6-0-calcium salt as an intermediate is as follows:
  • the mangoside-6-0-calcium salt of the present invention as an intermediate for the preparation of mangiferin-6-0-berberine salt in the specific method of the mangiferin-6-0-calcium salt solution concentration of 0.1 - 3%, preferably 1-2%;
  • concentration of the berberine hydrochloride solution is from 0.1 to 4%, preferably from 1 to 2%.
  • the mangoside-6-0-calcium salt of the present invention is used as an intermediate in the preparation of mangiferin-6-0-berberine salt in the specific method of mangiferin-6-0-calcium salt and berberine hydrochloride molar
  • the ratio is 0.5:1; the berberine hydrochloride can be replaced by berberine sulfate or other berberine medically acceptable salt.
  • Mangiferin-6-0-calcium salt molecular formula: C 38 H 34 0 22 Ca, pale yellowish green or light yellow powder, slightly soluble in water, dissolved in hot water, slightly soluble in dilute hydrochloric acid solution.
  • the structure is as follows:
  • the content of Ca in the mangiferin calcium salt was determined by plasma emission spectrometry: 4.5 ⁇ 10 4 mg/kg.
  • the mass spectrometry data showed that the molecular weight of the mangiferin calcium salt was 882, indicating that two molecules of mangiferin ions were linked to one molecule of calcium.
  • the content of Ca (calcium) in the manganyl calcium salt was determined by plasma emission spectrometry: 4.5 ⁇ 10 4 mg/kg (theoretical value 4.5 ⁇ 10 4 mg/kg).
  • the chemical structure of the mangiferin calcium salt is: 2 molecules of mangiferin-6-0 - combined with Ca 2+ to form mangiferin-6-0-calcium salt.
  • a crude mangiferin raw material (such as an extract having a mangiferin content of about 80% and 90%) can be used as an intermediate material for preparing a high-purity, stable, and convenient storage of mangiferin-6-0-calcium salt; Preparation of mangiferin-6-0-calcium salt from crude mangiferin raw material can greatly reduce the production cost (the price of crude mangiferin raw material with mangiferin content of 80%-90 ⁇ 3 ⁇ 4 is high purity mangiferin (content ⁇ 98%) One-third or even lower, peers can reduce environmental pressure.
  • mangiferin-6-0-calcium salt as an intermediate to prepare mangiferin-6-0-berberine salt, which can improve mangiferin
  • the purity of -6_0_ berberine salt simplifies the purification process of mangiferin-6-0-berberine salt (the purity of mangiferin berberine salt disclosed in WO2010/145192 A1 is ⁇ 99%, if more than 99% mango is obtained)
  • the berberine salt is further purified, and the preparation cost of the mangiferin-6-0-berberine salt is lowered.
  • Test Example 1 Results of physicochemical properties of mangiferin-6-0-berberine salt
  • the chemical shifts of C 7 and C 8b carbon atoms change significantly due to the de-shielding effect, and the chemical shift of C 6 is the largest; the chemical shifts of C 5 , C 8 , and c 8a carbon atoms have different degrees of change due to shielding effects. Among them, the C 8 and C 8a chemical shifts at the C 6 atomic position vary greatly.
  • mangiferin-6-0-berberine salt is formed.
  • Test Example 2 Quality inspection of mangiferin-6-0-berberine salt
  • Mangiferin-6-0-berberine salt was prepared by two preparation methods using mangiferin content of mangoside content of 80%, 90%, 98%, and mangosine-6 was obtained by different methods. -0-purine salt pure
  • [0066] Preparation of mangiferin into mangiferin-6-0-calcium salt, and then reacting mangiferin-6-0-calcium salt solution with berberine hydrochloride solution to prepare mangiferin-6-0-berberine Salt (referred to as calcium salt route, that is, the preparation method of mangiferin-6-0-berberine salt in the content of the present invention);
  • the mangiferin is prepared into a sodium salt solution, and directly reacted with a berberine hydrochloride solution to prepare a mangiferin-6-0-berberine salt (referred to as a sodium salt route, attached).
  • alkaline sodium salt or alkaline potassium salt is added to water to prepare an alkaline sodium salt solution or alkaline potassium salt solution, concentration
  • [0070] 2 is added mangiferin dissolved in dimethyl sulfoxide to form a mangiferin solution;
  • the berberine hydrochloride solution is fully mixed with the mangiferin-6-0-sodium salt solution or the mangiferin-6-0-potassium salt solution, the reaction is complete, the precipitate is precipitated, and filtered to obtain a solid matter;
  • the mangiferin of the present invention is a commercially available product (Xi'an Ruilin Biotechnology Co., Ltd., with corresponding extraction) Manufacturers of equipment can produce).
  • Berberine hydrochloride and berberine sulfate are all commercially available (Xi'an Xiaocao Plant Technology Co., Ltd.).
  • Reagents such as sodium bicarbonate, sodium carbonate, potassium hydrogencarbonate, potassium carbonate, dimethyl sulfoxide (D MSO), anhydrous calcium chloride, calcium chloride, calcium gluconate, calcium lactate, calcium ketocarboxylate, etc. Sale.
  • the water is added to the reactor, 2000 ml, sodium bicarbonate 0. lmol force into water to prepare a concentration of 0.4 ⁇ 3 ⁇ 4 (w / v) sodium bicarbonate solution; O.lmol mangiferin (content 90%) Add 127ml DMSO (the ratio of mangiferin to DMSO is 1:3 (w/v)) to dissolve and prepare to prepare mangiferin solution; slowly add mangiferin solution to sodium bicarbonate solution, stir well, keep warm at 80 °C Completely, filtered, and weighed 0.05 mol of anhydrous calcium chloride and 0.025 mol of calcium gluconate dissolved in 1000 ml of water.
  • the mixed solution of calcium chloride and calcium gluconate was added to the reaction solution of mangiferin, stirred thoroughly, cooled, and precipitated. Precipitation, to room temperature, allowed to stand overnight, the reaction solution was suction filtered; the precipitate was dissolved in water, filtered, the filtrate was cooled, the precipitate was precipitated, allowed to stand at room temperature overnight, suction filtered, and the precipitate was vacuum dried at 50 ° C, pulverized, lightly The yellow powdered mangiferin-6-0-calcium salt had a yield of 7 0.5%, and the sample purity was 99.6% as determined by HPLC.
  • the ratio of mangiferin to DMSO is 1:4 (w/v)) dissolved, made into mangiferin solution; slowly add mangiferin solution to sodium carbonate solution, stir well, keep the reaction at 100 °C, filter through Weigh 0.06mol of calcium gluconate into 100 ml of hot water to dissolve, add calcium gluconate solution to the mangiferin reaction solution, stir well, cool down, precipitate out, settle to room temperature, let stand overnight, and filter the reaction solution; The precipitate was dissolved in heated water, filtered, and the filtrate was cooled, and the precipitate was precipitated.
  • the ratio of mangiferin to DMSO is 1:5 (w/v)) dissolved, made into mangiferin solution; slowly add mangiferin solution to potassium carbonate solution, stir well, keep the reaction at 50 °C, filter through ; Weigh 0.07mol of calcium lactate and add 100ml of hot water Dissolving, adding calcium lactate solution to mangiferin reaction solution, stirring well, cooling, precipitation, dropping to room temperature, allowing to stand overnight, and filtering the reaction solution; the precipitate is dissolved in heated water, filtered, and the filtrate is cooled to precipitate.
  • Ml DMSO (the ratio of mangiferin to DMSO is 1:0.2 (w / v)) heated to dissolve, made into mangiferin solution; slowly add mangiferin solution to sodium bicarbonate solution, fully stirred, complete reaction at 90 ° C , filtered, spare; weigh 0.05mol of calcium chloride into 800ml of water to dissolve, add calcium chloride solution to the mangiferin reaction solution, stir well, cool down, precipitate precipitation, drop to room temperature, let stand overnight, the reaction solution Filtration; The precipitate is dissolved in heated water, filtered, the filtrate is cooled, the precipitate is precipitated, allowed to stand at room temperature overnight, suction filtered, and the precipitate is dried under vacuum at 55 ° C, and pulverized to obtain a light yellow powder of mangiferin-6-0-calcium salt. The rate was 73.2%, and the sample purity was 99.6% as determined by HPLC.
  • DMSO (the ratio of mangiferin to DMSO is l: l (w / v)) heated to dissolve, made into mangiferin solution; slowly add mangiferin solution to alkaline sodium salt solution, fully stirred, 95 ° C heat preservation reaction completely , spare; weigh anhydrous magnesium chloride O.lmol dissolved in 1500ml water, add calcium chloride solution to mangiferin reaction solution, charge Stirring, cooling, precipitation, dropping to room temperature, standing overnight, suctioning the reaction solution; the precipitate was dissolved in heated water, filtered, the filtrate was cooled, the precipitate was precipitated, allowed to stand at room temperature overnight, suction filtered, and the precipitate was vacuumed at 55 ° C. Drying and pulverization gave a pale yellow powder of mangiferin-6-0-calcium salt in a yield of 65.2%, and the sample purity was determined by HPLC to be 99.0 ⁇ 3 ⁇ 4.
  • the solid is dried under vacuum at 55 ° C, and pulverized to obtain an orange-yellow solid mangiferin-6-0-berberine salt.
  • the hydrate had a yield of 71.5%.
  • the sample purity was determined by HPLC to be 99.5%.
  • the base salt has a yield of 78.2%.
  • the sample purity was determined by HPLC to be 99.6%.
  • the preparation method of the compound of the present invention solves the environmental pressure caused by the use of a large amount of organic solvents and reduces the production cost of mannosides-6-0-berberine salt, thereby being more suitable for industrial production.

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  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne un sel de mangiférine-6-O-calcium et son procédé de préparation, et l'utilisation du sel de mangiférine-6-O-calcium comme intermédiaire dans la préparation d'un sel de mangiférine-6-O-berbérine.
PCT/CN2017/090489 2016-07-04 2017-06-28 Sel de mangiférine-6-o-calcium et son procédé de préparation et son utilisation WO2018006737A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CN201780027751.4A CN109475569B (zh) 2016-07-04 2017-06-28 一种芒果苷-6-o-钙盐及其制备方法与用途
JP2018567960A JP6783329B2 (ja) 2016-07-04 2017-06-28 マンギフェリン−６−ｏ−カルシウム塩、その調製方法及び使用方法
EP17823549.5A EP3479829A4 (fr) 2016-07-04 2017-06-28 Sel de mangiférine-6-o-calcium et son procédé de préparation et son utilisation
US16/231,960 US10538547B2 (en) 2016-07-04 2018-12-25 Mangiferin-6-O-calcium salt and preparation process thereof

Applications Claiming Priority (2)

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CN201610510307 2016-07-04
CN201610510307.5 2016-07-04

Related Child Applications (1)

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US16/231,960 Continuation US10538547B2 (en) 2016-07-04 2018-12-25 Mangiferin-6-O-calcium salt and preparation process thereof

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WO2018006737A1 true WO2018006737A1 (fr) 2018-01-11

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US (1) US10538547B2 (fr)
EP (1) EP3479829A4 (fr)
JP (1) JP6783329B2 (fr)
CN (1) CN109475569B (fr)
WO (1) WO2018006737A1 (fr)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1919857A (zh) * 2006-08-24 2007-02-28 广西中医学院 水溶性芒果苷单钠盐的制备方法及其应用
CN101066275A (zh) * 2007-06-12 2007-11-07 广西中医学院 芒果苷－小檗碱组合物
CN101108869A (zh) * 2006-07-21 2008-01-23 徐广爱 一种芒果苷盐及其制备方法与用途
WO2008061480A1 (fr) * 2006-11-24 2008-05-29 Hainan Deze Drug Research Co., Ltd Nouveaux sels de calcium de mangiférine, leur procédé de preparation et leur utilisation
CN101229181A (zh) * 2006-09-12 2008-07-30 徐广爱 具有糖尿病及其并发症治疗作用的药物组合物
CN101461819A (zh) * 2007-12-20 2009-06-24 海南德泽药物研究有限公司 芒果苷钙盐作为过氧化物酶增殖物激活受体激动剂的用途
CN101848922A (zh) * 2007-11-22 2010-09-29 海南德泽药物研究有限公司 一种新的芒果苷钙盐及其制备方法与用途
CN101919839A (zh) * 2009-06-12 2010-12-22 海南德泽药物研究有限公司 芒果苷钙盐作为ampk激动剂的用途
CN101921270A (zh) * 2009-06-16 2010-12-22 海南德泽药物研究有限公司 一种芒果苷小檗碱盐及其制备方法与用途

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7776915B2 (en) * 2005-03-24 2010-08-17 Tracie Martyn International, Llc Topical formulations and methods of use
EP2220103B1 (fr) * 2007-11-22 2015-04-08 Hainan Deze Drug Research Co., Ltd Nouveaux sels de calcium de mangiférine, leur procédé de préparation et leur utilisation
RU2014129753A (ru) * 2011-12-21 2016-02-10 Колгейт-Палмолив Компани Шанхуо и секреторный иммуноглобулин слюны
CN104558070B (zh) * 2013-10-14 2017-10-24 北京大学 新芒果苷的化学合成方法及中间体化合物
CN103816153A (zh) * 2013-12-10 2014-05-28 无锡万全医药技术有限公司 化合物dzcy06在制备治疗糖尿病药物中的用途
EP3243823B1 (fr) * 2015-01-07 2020-12-16 Changzhou Deze Medical Science Co., Ltd. Sel de mangiférine-6-o-berbérine, son procédé de préparation et son utilisation

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101108869A (zh) * 2006-07-21 2008-01-23 徐广爱 一种芒果苷盐及其制备方法与用途
CN1919857A (zh) * 2006-08-24 2007-02-28 广西中医学院 水溶性芒果苷单钠盐的制备方法及其应用
CN101229181A (zh) * 2006-09-12 2008-07-30 徐广爱 具有糖尿病及其并发症治疗作用的药物组合物
WO2008061480A1 (fr) * 2006-11-24 2008-05-29 Hainan Deze Drug Research Co., Ltd Nouveaux sels de calcium de mangiférine, leur procédé de preparation et leur utilisation
CN101066275A (zh) * 2007-06-12 2007-11-07 广西中医学院 芒果苷－小檗碱组合物
CN101848922A (zh) * 2007-11-22 2010-09-29 海南德泽药物研究有限公司 一种新的芒果苷钙盐及其制备方法与用途
CN101461819A (zh) * 2007-12-20 2009-06-24 海南德泽药物研究有限公司 芒果苷钙盐作为过氧化物酶增殖物激活受体激动剂的用途
CN101919839A (zh) * 2009-06-12 2010-12-22 海南德泽药物研究有限公司 芒果苷钙盐作为ampk激动剂的用途
CN101921270A (zh) * 2009-06-16 2010-12-22 海南德泽药物研究有限公司 一种芒果苷小檗碱盐及其制备方法与用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3479829A4 *

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JP2019519569A (ja) 2019-07-11
CN109475569A (zh) 2019-03-15
JP6783329B2 (ja) 2020-11-11
US10538547B2 (en) 2020-01-21
CN109475569B (zh) 2021-10-19
US20190127410A1 (en) 2019-05-02
EP3479829A1 (fr) 2019-05-08

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